IMP-1 inhibits renal cell carcinoma 786-O cell growth by targeting EphrinB2 signaling pathway

Abstract EphrinB2 plays a critical role in tumor growth. In this study, we studied the antitumor activity of imperatorin derivative IMP-1 in renal cell carcinoma (RCC) by regulating EphrinB2 pathway.. Results showed that IMP-1 inhibited the proliferation of 786-O cells in a dose- and time-dependent manner. More importantly, knockdown and transfection of EphrinB2 altered the inhibitory effect of IMP-1 on the activity of 786-O cells. IMP-1 arrested 786-O cell cycle at G0/G1 phase by decreasing the expression of cyclin D1 and cyclin E. Moreover, IMP-1 regulated Bcl-2 family proteins' expression, thus inducing apoptosis of 786-O cells. IMP-1 down-regulated the expression of EphrinB2, Syntenin1 and PICK1. Then, IMP-1 decreased the phosphorylation of Erk1/2 and AKT. In all, IMP-1 could regulate the EphrinB2 pathway in order to inhibit 786-O cell growth by arresting the cell cycle at G0/G1 phase and inducing cell apoptosis. Thus, IMP-1 may present as a potential strategy for RCC treatment.

RNA-binding protein and tumor biotherapy: new opportunities and strategies / 中国肿瘤生物治疗杂志

@#RNA结合蛋白（RBP）由于其独特的生物学功能，目前已经成为肿瘤生物治疗相关靶点筛选的宠儿，很可能为肿瘤生物治疗带来新的机遇。RBP能调控肿瘤细胞及肿瘤微环境免疫细胞和间质细胞的DNA-RNA-蛋白质相互作用网络，进而广泛影响肿瘤发生发展、抗肿瘤免疫应答及肿瘤免疫逃逸过程，目前RBP相关肿瘤生物治疗的研发，主要聚焦在治疗性疫苗、免疫细胞治疗、表观调控治疗等方面，部分研发成果已处于临床试验阶段。随着新理论、新技术的发展以及研究模式的创新，靶向RBP的治疗逐渐摆脱了既往靶向难、疗效欠佳的困局，迎来了新的机遇，通过改良精准靶向和优化组合用药等新策略，为肿瘤生物治疗注入了新的活力，对精准个体化医疗的发展具有重要意义。

Interactions between gut microbiota and berberine,a necessary procedure to understand the mechanisms of berberine / 药物分析学报

Berberine(BBR),an isoquinoline alkaloid,has been found in many plants,such as Coptis chinensis Franch and Phellodendron chinense Schneid.Although BBR has a wide spectrum of pharmacological effects,its oral bioavailability is extremely low.In recent years,gut microbiota has emerged as a cynosure to un-derstand the mechanisms of action of herbal compounds.Numerous studies have demonstrated that due to its low bioavailability,BBR can interact with the gut microbiota,thereby exhibiting altered pharma-cological effects.However,no systematic and comprehensive review has summarized these interactions and their corresponding influences on pharmacological effects.Here,we describe the direct interactive relationships between BBR and gut microbiota,including regulation of gut microbiota composition and metabolism by BBR and metabolization of BBR by gut microbiota.In addition,the complex interactions between gut microbiota and BBR as well as the side effects and personalized use of BBR are discussed.Furthermore,we provide our viewpoint on future research directions regarding BBR and gut microbiota.This review not only helps to explain the mechanisms underlying BBR activity but also provides support for the rational use of BBR in clinical practice.

Efficacy and safety of single-agent PD-1 inhibitors versus chemotherapy in second-line treatment of advanced esophageal squamous cell carcinoma: a Meta-analysis / 中国肿瘤生物治疗杂志

@# [摘 要] 目的：系统评价单药程序性死亡受体1（PD-1）抑制剂对比化疗二线治疗晚期食管鳞状细胞癌（ESCC）患者的疗效及安全性，以期为临床决策提供最佳循证医学证据。方法：计算机检索The Cochrane Library、Web of Science、PubMed、EMbase、CNKI和万方等数据库，同时检索J Clin Oncol、N England Oncol、Lancet Oncol等杂志以及ASCO、EMSO会议摘要中有关单药PD-1抑制剂对比传统化疗二线治疗晚期ESCC患者的临床随机对照试验（RCT），筛选文献，提取资料，采用RevMan5.3进行Meta分析。结果：共纳入5项RCT研究（1 732例患者）。与化疗组比，单药PD-1抑制剂二线治疗晚期ESCC可显著延长患者的总生存期（OS）（HR＝0.75，95% CI：0.67~0.83，P<0.000 01）。以PD-L1不同表达程度进行亚组分析，在延长OS方面，TPS<1%时，单药PD-1抑制剂二线治疗晚期ESCC无明显优势；而TPS≥1%、TPS<5%、TPS≥5%、TPS<10%、TPS≥10%时，单药PD-1抑制剂二线治疗均可显著延长晚期ESCC患者的OS，且PD-L1表达程度越高，疗效获益更显著。然而，与化疗组比，单药PD-1抑制剂在延长晚期ESCC患者的无进展生存期（PFS）（HR＝0.93，95% CI：0.79~1.10，P=0.41）及提高客观有效率（ORR）（RR＝1.62，95% CI：0.95~2.74，P=0.07）等方面，差异均无统计学意义。但单药PD-1抑制剂组3~5级不良反应发生率低（RR＝0.37，95% CI：0.28~0.50，P<0.000 01）。结论：单药PD-1抑制剂二线治疗晚期ESCC患者可显著延长患者的OS；PD-L1高表达者PD-1抑制剂可作为二线治疗的优先选择，且具有良好的安全性。 , , , , , ()

Effect of lncRNA MAFG-AS1 regulating miR-532-3p expression on glycolysis of lung cancer A549 cells / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨lncRNA MAFG反义RNA1（MAFG-AS1）调控miR-532-3p表达对肺癌A549细胞糖酵解的影响。方法：用qPCR法检测人肺癌A549细胞和正常肺上皮细胞BEAS-2B中MAFG-AS1和miR-532-3p的表达水平。利用脂质体介导转染技术，分别构建MAFG-AS1表达下调和miR-532-3p过表达的A549细胞，用分光光度法检测细胞培养上清中葡萄糖消耗量与乳酸含量，qPCR和WB法分别检测细胞中M2型丙酮酸激酶（pyruvate kinase M2，PKM2）、己糖激酶2（hexokinase 2，HK2） mRNA和蛋白的表达水平。用双荧光素酶报告基因实验验证MAFG-AS1与miR-532-3p的靶向关系，观察MAFG-AS1和miR-532-3p同时低表达对A549细胞葡萄糖及乳酸含量和PKM2、HK2表达的影响。结果：与BEAS-2B细胞比较，A549细胞中MAFG-AS1表达上调而miR-532-3p表达下调（均P<0.01）。下调MAFG-AS1或miR-532-3p过表达均可降低A549细胞葡萄糖消耗量及乳酸含量，并抑制PKM2、HK2 mRNA和蛋白的表达（均P<0.01）。miR-532-3p可与MAFG-AS1靶向结合抑制野生型MAFG-AS1细胞的荧光素酶活性（P<0.01），下调MAFG-AS1可使A549细胞中miR-532-3p表达升高（P<0.01）。miR-532-3p低表达可逆转MAFG-AS1表达下调对细胞葡萄糖消耗量及乳酸含量和PKM2、HK2表达的影响（均P<0.01）。结论：下调MAFG-AS可通过促进miR-532-3p表达而抑制肺癌A549细胞糖酵解。

High expression of nucleophosmin is closely related to the grade and invasion of colorectal cancer

This study explores the differential protein expression in the colorectal cancer (CRC) patients to validate a new biomarker for tumor progression. CRC tissues and their adjacent non-cancerous tissues were analyzed by two-dimensional LC/MS/MS. Nucleophosmin 1 (NPM1) was selected and confirmed its differential expression by Western blot. Immunohistological staining of NPM1 in tissues was performed to validate its correlation with clinicopathologic parameters of CRC patients. There were 39 candidates with significant difference between cancerous tissues and their adjacent non-cancerous tissues, which included 19 increased proteins and 20 decreased proteins in CRC samples. Especially, NPM1 was correlated with poor differentiation, and lymph node metastasis according to the analysis of patients’ clinicopathologic parameters. Increased expression of NPM1 can be as a critical biomarker for clinical diagnosis of tumor progression of CRC patients.

Efficacy and safety of ramucircumab in treatment of advanced non-small cell lung cancer：a Meta analysis / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To systematically evaluate the efficacy and safety of ramcircumab in the treatment of advanced non-small cell lung cancer (NSCLC) by a Meta-analysis. Methods: The randomized controlled clinical trials of ramcircumab in the treatment of advanced non-small cell lung cancer were retrieved from Cochrane Library (2017, Issue 8), Web of Science, Pubmed, EMbase, Wanfang Database, CNKI, CBM, Chinese Science and TechnologyAcademic Journal andASCO, ESMO main conference database, with the enddate of September 1, 2017. Two independent reviewers selected the literatures, extracted the data, and assessed the quality of the included studies. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse reactions in NSCLC patients of ramcircumab group and control group were analyzed by RevMan5.3 software. Results: Three RCTs were finally included in this meta-analysis. A total of 1 545 NSCLC patients were enrolled, including 777 in ramcircumab group and 768 in control group. The PFS and OS of NSCLC patients in the ramcircumab group were all better than those of the control group (HR=0.77,95%CI[0.69-0.85], P<0.01; HR=0.88, 95%CI[0.78-0.99], P<0.05). However, there was no statistically significant difference in the ORR between the ramcircumab group and the control group (RR=1.33, 95%CI[0.68-2.61], P>0.05). Compared with docetaxel single-agent second-line treatment, Ramcircumab combined with docetaxel can prolong PFS and OS of advanced NSCLC patients (HR=0.77, 95%CI[0.69-0.86], P< 0.01; HR=0.86, 95%CI [0.76-0.98], P<0.05). The most serious adverse reaction in the ramcircumab group was hypertension (RR=3.33, 95%CI[1.83-6.05], P<0.01); whereas the incidences of nausea, vomiting, diarrhea, loss of appetite, fatigue, proteinuria, neutropenia, leukopenia, thrombocytopenia, and bleeding etc. showed no significant differences between the two groups (all P>0.05). Conclusion: Ramcircumab can prolong PFS and OS of patients with advanced NSCLC. The main adverse reaction is hypertension.

Relationship between interleukin-6 -572 gene polymorphism and aggressive periodontitis in Chinese / 口腔疾病防治

Objective@#To investigate the association between interleukin-6 -572 gene polymorphism and aggressive periodontitis. @*Methods @#A case-control study involved 83 patients with aggressive periodontitis (AgP) and 69 health controls was held, and the genotype and allele distributions of interleukin-6 -572 gene polymorphism were analyzed by PCR-RFLP. @* Results @#There was statistically significant differences in the genotype distribution by the chi-square test in the two groups (χ2 = 13.710, P=0.001). The distribution of allele frequencies in AgP group was statistically different (χ2=13.213, P < 0.001) from the healthy control group, and the OR for the G allele is 2.988 (95%CI: 1.634-5.465) when compared with the C allele.@*Conclusion@#IL-6 -572 gene polymorphism is associated with the susceptibility to AgP in Chinese Han population of Guangdong, and the IL-6 -572 G allele might be a risk factor of the genetic susceptibility to AgP.

Association between MTHFR A1298C Polymorphism and Male Infertility: A Meta-analysis / 华中科技大学学报（医学）（英德文版）

There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the risk of male infertility.However,the results obtained were inconsistent.Therefore,we performed a meta-analysis to further examine the association between the MTHFR A1298C polymorphism and male infertility.A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to January 15th,2016.A total of 20 studies with 4293 cases and 4507 controls were included.An odds ratio (OR) and a 95％ confidence interval (95％ CI) were calculated to assess the strength of the association.A cumulative meta-analysis,sensitivity analysis and assessment of the publication bias were also performed in this study.The results showed that in the overall analysis,the association between the MTHFR A1298C polymorphism and male infertility was not significant.A stratified analysis by ethnicity revealed a significant increase in the risk of male infertility in the Asian population with the MTHFR A1298C polymorphism (especially in the heterozygote model:OR=l.20,95％ CI=1.01-1.44,P=0.994;the dominant model:OR=1.23,95％ CI=1.04-1.45,P=0.996;and the allele model:OR=l.20,95％ CI=1.04-1.39,P=0.985) but not in the Caucasian population.In the stratified analyses,no significant association was observed between the different types of male infertility.This meta-analysis suggests the MTHFR A1298C polymorphism may be a potential risk factor for male infertility,especially in the Asian population.

Interferon-gamma-induced local leukocytoclastic vasculitis at the subcutaneous injection site

Abstract Cutaneous reactions associated with interferons (IFNs) treatment are either localized or generalized. The most common presentation of localized reactions at IFNs injection site is usually an erythematous patch or plaque. Local leukocytoclastic vasculitis presenting with cutaneous necrosis is extremely rare. We report a 19-year-old man with hepatitis B who had local leukocytoclastic vasculitis induced by interferon-gama injection at the injection site. After changing the injection sites and using the combined treatment of prednisone and colchicine, the previous lesion healed and no other cutaneous lesion occurred. We also made a mini review of such cases.

Role of Transforming Growth Factor-β1 in the Process of Fibrosis of Denervated Skeletal Muscle / 华中科技大学学报（医学）（英德文版）

In order to investigate the biological function of transforming growth factor-β1 (TGF-β1)during fibrosis in denervated skeletal muscle,we recruited sciatic nerve injury model of SD rats in which denervated gastrocnemius was isolated for analysis.At different time points after operation,denervated muscle was examined by several methods.Masson trichrome staining showed morphological changes of denervated skeletal muscle.Quantitative RT-PCR detected the rapid increase of TGF-β1 expression at mRNA level after nerve injury.It was found that a peak of TGF-β1 mRNA expression appeared one week post-operation.The expression of collagen Ⅰ (COL Ⅰ ) mRNA was up-regulated in the nerve injury model as well,and reached highest level two weeks post-injury.Immunoblot revealed similar expression pattern of TGF-β1 and COL Ⅰ in denervated muscles at protein level.In addition,we found that the area of the gastrocnemius muscle fiber was decreased gradually along with increased interstitital fibrosis.Interestingly,this pathological change could be prevented,at least partly,by local injection of TGF-β1 antibodies,which could be contributed to the reduced production of COL Ⅰ by inhibiting function of TGF-β1.Taken together,in this study,we demonstrated that the expression of TGF-β1 was increased significantly in denervated skeletal muscle,which might play a crucial role during muscle fibrosis after nerve transection.